The objectives of this research program are 1) to define the neurological mechanisms operating at the hypothalamic level to control vasopressin (VP) release and 2) to ascertain the relationship of these control mechanisms to the osmotic regulation of VP release. Two culture systems will be used in these studies: organ cultured explants of the adult rat hypothalamo-neurohypophyseal system (HNS) and primary dispersed monolayer co-cultures of anterior hypothalamus (including the supraoptic nucleus) with either pituicytes or ventral medullary neurons (including the Al catecholamine neurons.) The effect of various agents on VP release from these cultures will be monitored with a VP radioimmunoassay. Norepinephrine release from the dispersed cultures containing Al neurons will be monitored with HPLC techniques. Specific agents to be evaluated are neurotransmitters, centrally active brain peptides, prostaglandins, and agents used clinically in the treatment of abnormalities of VP release. These studies will provide information on the mechanisms which allow a single target neuron to integrate multiple afferent signals. They will also provide basic information about the physiological mechanisms involved in the osmotic control of VP release, and thereby, they may provide the basis for understanding clinically observed abnormalities in VP release.